IMPORTANCE Unrealistic patient expectations of the benefits and harms of interventions can influence decision making and may be contributing to increasing intervention uptake and health care costs. OBJECTIVE To systematically review all studies that have quantitatively assessed patients' expectations of the benefits and/or harms of any treatment, test, or screening test. EVIDENCE REVIEW A comprehensive search strategy was used in 4 databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO) up to June 2013, with no language or study type restriction.We also ran cited reference searches of included studies and contacted experts and study authors. Two researchers independently evaluated methodological quality and extracted participants' estimates of benefit and harms and authors' contemporaneous estimates. FINDINGS Of the 15 343 records screened, 36 articles (from 35 studies) involving a total of 27 323 patients were eligible. Fourteen studies focused on a screen, 15 on treatment, 3 a test, and 3 on treatment and screening. More studies assessed only benefit expectations (22 [63%]) than benefit and harm expectations (10 [29%]) or only harm (3 [8%]). Fifty-four outcomes (across 32 studies) assessed benefit expectations: of the 34 outcomes with overestimation data available, the majority of participants overestimated benefit for 22 (65%) of them. For 17 benefit expectation outcomes, we could not calculate the proportion of participants who overestimated or underestimated, although for 15 (88%) of these, study authors concluded that participants overestimated benefits. Expectations of harm were assessed by 27 outcomes (across 13 studies): underestimation data were available for 15 outcomes and the majority of participants underestimated harm for 10 (67%) of these. A correct estimation by at least 50% of participants only occurred for 2 outcomes about benefit expectations and 2 outcomes about harm expectations. CONCLUSIONS AND RELEVANCE The majority of participants overestimated intervention benefit and underestimated harm. Clinicians should discuss accurate and balanced information about intervention benefits and harms with patients, providing the opportunity to develop realistic expectations and make informed decisions.